Cell Density Control of Staphylococcal Virulence Mediated by an Octapeptide Pheromone

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Dec 19

PMID 8618843

Citations 250

Authors

G Ji

R C Beavis

R P Novick

Affiliations

Soon will be listed here.

Abstract

Some bacterial pathogens elaborate and secrete virulence factors in response to environmental signals, others in response to a specific host product, and still others in response to no discernible cue. In this study, we have demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself. The octapeptide activates expression of the agr locus, a global regulator of the virulence response. This response involves the reciprocal regulation of genes encoding surface proteins and those encoding secreted virulence factors. As cells enter the postexponential phase, surface protein genes are repressed by agr and secretory protein genes are subsequently activated. The intracellular agr effector is a regulatory RNA, RNAIII, whose transcription is activated by an agr-encoded signal transduction system for which the octapeptide is the ligand.

Citing Articles

Structural characteristics, functions, and counteracting strategies of biofilms in .

Xia Y, Hu Z, Jin Q, Chen Q, Zhao C, Qiang R Comput Struct Biotechnol J. 2025; 27:488-500.

PMID: 39916696 PMC: 11799891. DOI: 10.1016/j.csbj.2025.01.021.

: Current perspectives on molecular pathogenesis and virulence.

Girma A Cell Surf. 2025; 13:100137.

PMID: 39758277 PMC: 11699754. DOI: 10.1016/j.tcsw.2024.100137.

Biofilm formation by is triggered by a drop in the levels of a cyclic dinucleotide.

Syed A, Baral R, Van Vlack E, Gil-Marques M, Lenhart T, Hooper D Proc Natl Acad Sci U S A. 2024; 121(52):e2417323121.

PMID: 39680756 PMC: 11670122. DOI: 10.1073/pnas.2417323121.

Recent developments in preventing catheter-related infections based on biofilms: A comprehensive review.

So B, Kim J, Jo J, So H Biomicrofluidics. 2024; 18(5):051506.

PMID: 39397894 PMC: 11470810. DOI: 10.1063/5.0195165.

Inhibitory Effects of Lactobionic Acid on Biofilm Formation and Virulence of .

Kang S, Yang Y, Hou W, Zheng Y Foods. 2024; 13(17).

PMID: 39272546 PMC: 11395522. DOI: 10.3390/foods13172781.

References

Chang S, Cohen S . High frequency transformation of Bacillus subtilis protoplasts by plasmid DNA. Mol Gen Genet. 1979; 168(1):111-5. DOI: 10.1007/BF00267940. View

OCALLAGHAN C, Morris A, Kirby S, Shingler A . Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972; 1(4):283-8. PMC: 444209. DOI: 10.1128/AAC.1.4.283. View

Nixon B, Ronson C, Ausubel F . Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genes ntrB and ntrC. Proc Natl Acad Sci U S A. 1986; 83(20):7850-4. PMC: 386820. DOI: 10.1073/pnas.83.20.7850. View

Kornblum J, Projan S, Moghazeh S, Novick R . A rapid method to quantitate non-labeled RNA species in bacterial cells. Gene. 1988; 63(1):75-85. DOI: 10.1016/0378-1119(88)90547-1. View

Peng H, Novick R, Kreiswirth B, Kornblum J, Schlievert P . Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol. 1988; 170(9):4365-72. PMC: 211451. DOI: 10.1128/jb.170.9.4365-4372.1988. View

Dunlap P, RAY J . Requirement for autoinducer in transcriptional negative autoregulation of the Vibrio fischeri luxR gene in Escherichia coli. J Bacteriol. 1989; 171(6):3549-52. PMC: 210084. DOI: 10.1128/jb.171.6.3549-3552.1989. View

Janzon L, Lofdahl S, Arvidson S . Identification and nucleotide sequence of the delta-lysin gene, hld, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol Gen Genet. 1989; 219(3):480-5. DOI: 10.1007/BF00259623. View

Janzon L, Arvidson S . The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus. EMBO J. 1990; 9(5):1391-9. PMC: 551825. DOI: 10.1002/j.1460-2075.1990.tb08254.x. View

Novick R . Genetic systems in staphylococci. Methods Enzymol. 1991; 204:587-636. DOI: 10.1016/0076-6879(91)04029-n. View

10.

Mekalanos J . Environmental signals controlling expression of virulence determinants in bacteria. J Bacteriol. 1992; 174(1):1-7. PMC: 205668. DOI: 10.1128/jb.174.1.1-7.1992. View

11.

Hillenkamp F, Karas M, Beavis R, Chait B . Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem. 1991; 63(24):1193A-1203A. DOI: 10.1021/ac00024a002. View

12.

PARKINSON J, Kofoid E . Communication modules in bacterial signaling proteins. Annu Rev Genet. 1992; 26:71-112. DOI: 10.1146/annurev.ge.26.120192.000443. View

13.

Zhang L, Murphy P, Kerr A, Tate M . Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones. Nature. 1993; 362(6419):446-8. DOI: 10.1038/362446a0. View

14.

Long S, Staskawicz B . Prokaryotic plant parasites. Cell. 1993; 73(5):921-35. DOI: 10.1016/0092-8674(93)90271-q. View

15.

Jones S, Yu B, Bainton N, Birdsall M, Bycroft B, Chhabra S . The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa. EMBO J. 1993; 12(6):2477-82. PMC: 413484. DOI: 10.1002/j.1460-2075.1993.tb05902.x. View

16.

Novick R, Ross H, Projan S, Kornblum J, Kreiswirth B, Moghazeh S . Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 1993; 12(10):3967-75. PMC: 413679. DOI: 10.1002/j.1460-2075.1993.tb06074.x. View

17.

Magnuson R, Solomon J, Grossman A . Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell. 1994; 77(2):207-16. DOI: 10.1016/0092-8674(94)90313-1. View

18.

Balaban N, Novick R . Autocrine regulation of toxin synthesis by Staphylococcus aureus. Proc Natl Acad Sci U S A. 1995; 92(5):1619-23. PMC: 42571. DOI: 10.1073/pnas.92.5.1619. View

19.

Novick R, Projan S, Kornblum J, Ross H, Ji G, Kreiswirth B . The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol Gen Genet. 1995; 248(4):446-58. DOI: 10.1007/BF02191645. View

20.

NOVICK R . Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology. 1967; 33(1):155-66. DOI: 10.1016/0042-6822(67)90105-5. View